The goal is to develop a long-term human myeloma cell line that will provide valuable substrates for subcategorizing B-cell malignancies, for generating human-derived monoclonal antibodies that may become major diagnostic and/or therapeutic tools, and for understanding the normal and abnormal process of human B-cell maturation. A long-term plasma cell line, derived from a patient with multiple myeloma, has been characterized, subcloned, and used as antigen in the genesis of mouse monoclonal antibodies directed against human plasma cells and/or human myeloma cells. The role of growth and differentiation factors in the maintenance of the long-term line has been explored and attempts made to utilize such factors in establishing growth of other human myeloma cells. Eight additional human plasma cell lines have been developed one of which is a nonsecretor. These lines grow in nude mice and secrete immunoglobulin. Some successful human-human hybridizations have occurred. (2)